(3RS)-3-[(2SR)-(2-cyclopentyl-2-hydroxy-2-phenylacetyl)oxy]-1,1-dimethylpyrrolidinium bromide, also known as glycopyrronium bromide (compound I) is an M3 antagonist, developed by Sosei R&D in collaboration with Vectura for the treatment of chronic obstructive pulmonary disease (COPD) and asthma. Glycopyrronium bromide is a quaternary ammonium salt (ionic compound) and it is completely ionized between pH 1 and 14. It is a racemic mixture of the 3R,2S and 3S,2R stereoisomers. No optical rotation is seen in solution. Glycopyrronium bromide, which is depicted below, is marketed under the tradename Seebri Breezhaler®.

A number of methods of synthesis of glycopyrronium bromide have been reported up to date. Glycopyrronium bromide was first disclosed by the U.S. Pat. No. 2,956,062 to Robins Company, which describes a synthetic approach to the preparation of glycopyrronium bromide, similar molecules and also pharmaceutical composition containing them.
The Finnish patent FI49713 also describes a process for the preparation of the erythro-glycopyrronium bromide. In this patent the enantiomeric forms of glycopyrronium bromide are obtained by the preparation of the intermediate 5-nitroisophthalic acid salts from the mixture of threo- and erythro-1-methyl-3-pyrrolidinyl alpha-cyclopentyl mandelates. These salts are crystalline and may be separated due to their different solubility by digesting them with a suitable organic solvent. Nevertheless, the quality obtained for the 5-nitroisophthalic salts to obtain the final product glycopyrronium bromide is not an acceptable quality for pharmaceutical use as inhaler.
These disadvantages also increase the cost of the final glycopyrronium bromide and the pharmaceutical compositions containing it. In view of the pharmaceutical value of this compound, it is important to obtain an efficient and safe process for the preparation of glycopyrronium bromide in high yields, which can be applied at an industrial scale with low energy and costs. Therefore, there is a need to develop an improved industrially feasible process for the preparation of glycopyrronium bromide, which is more efficient, and can provide glycopyrronium bromide in high chemical and enantiomeric purity and yield and which can be easily performed at industrial scale.